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  Crosstalk between PKCzeta and the IL4/Stat6 pathway during T-cell-mediated hepatitis

Duran, A., Rodriguez, A., Martin, P., Serrano, M., Flores, J. M., Leitges, M., et al. (2004). Crosstalk between PKCzeta and the IL4/Stat6 pathway during T-cell-mediated hepatitis. EMBO Journal, 23(23), 4595-4605. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15526032.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-EBC4-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-095B-B
Genre: Journal Article

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Duran, A., Author
Rodriguez, A., Author
Martin, P., Author
Serrano, M., Author
Flores, J. M., Author
Leitges, M.1, Author              
Diaz-Meco, M. T., Author
Moscat, J., Author
Affiliations:
1Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society, ou_persistent34              

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 Abstract: PKCzeta is required for nuclear factor kappa-B (NF-kappaB) activation in several cell systems. NF-kappaB is a suppressor of liver apoptosis during development and in concanavalin A (ConA)-induced T-cell-mediated hepatitis. Here we show that PKCzeta-/- mice display inhibited ConA-induced NF-kappaB activation and reduced damage in liver. As the IL-4/Stat6 pathway is necessary for ConA-induced hepatitis, we addressed here the potential role of PKCzeta in this cascade. Interestingly, the loss of PKCzeta severely attenuated serum IL-5 and liver eotaxin-1 levels, two critical mediators of liver damage. Stat6 tyrosine phosphorylation and Jak1 activation were ablated in the liver of ConA-injected PKCzeta-/- mice and in IL-4-stimulated PKCzeta-/- fibroblasts. PKCzeta interacts with and phosphorylates Jak1 and PKCzeta activity is required for Jak1 function. In contrast, Par-4-/- mice have increased sensitivity to ConA-induced liver damage and IL-4 signaling. This unveils a novel and critical involvement of PKCzeta in the IL-4/Stat6 signaling pathway in vitro and in vivo.

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 Dates: 2004-11-24
 Publication Status: Published in print
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 Rev. Method: Peer
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Title: EMBO Journal
Source Genre: Journal
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Pages: - Volume / Issue: 23 (23) Sequence Number: - Start / End Page: 4595 - 4605 Identifier: -